N-Terminal-Dependent Protein Degradation and Targeting Cancer Cells

Author(s): Mohamed A. Eldeeb*

Journal Name: Anti-Cancer Agents in Medicinal Chemistry
(Formerly Current Medicinal Chemistry - Anti-Cancer Agents)

Volume 21 , Issue 2 , 2021

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Graphical Abstract:


Intracellular protein degradation is mediated selectively by the Ubiquitin-Proteasome System (UPS) and autophagic-lysosomal system in mammalian cells. Many cellular and physiological processes, such as cell division, cell differentiation, and cellular demise, are fine-tuned via the UPS-mediated protein degradation. Notably, impairment of UPS contributes to human disorders, including cancer and neurodegeneration. The proteasome- dependent N-degron pathways mediate the degradation of proteins through their destabilizing aminoterminal residues. Recent advances unveiled that targeting N-degron proteolytic pathways can aid in sensitizing some cancer cells to chemotherapeutic agents. Furthermore, interestingly, exploiting the N-degron feature, the simplest degradation signal in mammals, and fusing it to a ligand specific for Estrogen-Related Receptor alpha (ERRa) has demonstrated its utility in ERRa knockdown, via N-terminal dependent degradation, and also its efficiency in the inhibition of growth of breast cancer cells. These recent advances uncover the therapeutic implications of targeting and exploiting N-degron proteolytic pathways to curb growth and migration of cancer cells.

Keywords: Cancer cell death, apoptosis, N-degron, N-end rule, protein degradation, proteolysis, ubiquitin, proteasome, PROTACS.

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Article Details

Year: 2021
Published on: 31 December, 2020
Page: [231 - 236]
Pages: 6
DOI: 10.2174/1871520620666200819112632
Price: $65

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